Gatton College of Pharmacy researcher builds a Trojan horse to battle cancer

JOHNSON CITY (April 12, 2013) – It is a form of subterfuge used by the ancient Greeks in time of war, and one still used today, in the virtual world, by computer hackers.

At East Tennessee State University’s Bill Gatton College of Pharmacy, Dr. Zachary Walls is busy building a Trojan horse, too. But Walls, an assistant professor in the ETSU Department of Pharmaceutical Sciences, doesn’t plan to hijack e-mail accounts or steal personal information on the internet. One might say he isn’t trying to win a war, either – except that this Trojan horse is a tool in the fight against cancer.

Drugs that are used in chemotherapy treatments for cancer patients often face hurdles on the human cellular level that diminish their effectiveness – getting those drugs past the cellular membrane and into the cell is the challenge. To deliver those drugs into the cell, they are packaged within in a synthetic, molecular vessel called a liposome, which will pass through cellular walls. But it’s not always an efficient delivery system, Walls said, as the process can lead to degradation of the drugs and contribute to treatments that are not target-specific.

In his ETSU lab, Walls is turning to a notorious bacterium for help: Listeria monocytogenes.

“We’re using Listeria as a sort of Trojan horse,” Walls said.

That bacterium is most often associated with the food-borne illness listeriosis. A protein component of Listeria, called Listeriolysin O, contributes to its virulence but also enables the breaching of human cells without damaging the cellular membrane. Walls and his research collaborators have isolated a mutated form of Listeriolysin O that blunts its negative properties while drawing upon its positive transport qualities. Walls’ novel approach resulted in a grant proposal, “Listeriolysin O-Liposomes, for the Treatment of Drug Resistant Cancer,” that was recognized by the American Association of Colleges of Pharmacy (AACP) with a 2012-13 New Investigator Award. Walls was one of only 17 researchers who received the New Investigator grant this year.

“Most bacteria reproduce outside of cells,” Walls said, “but Listeria is different; it likes to reproduce inside cells, and it has a mechanism to escape the endosomal membrane. It contains a protein that will poke holes in the endosome to allow all the drugs inside the liposome to be released inside the cell.”

Before he joined the ETSU faculty in 2011, Walls trained as a postdoctoral researcher at the University of Michigan, where he began working with Listeria monocytogenes as a transport model. He received his doctorate in molecular and medical pharmacology from the University of California at Los Angeles.

Walls is hopeful this approach could lead to treatments that are more effective and could be more specific in targeting diseased cells. He expressed gratitude to the AACP for funding support, as well as his colleagues at the university, the ETSU Research Development Committee and the Office of Research and Sponsored Programs Administration.